Cardiopulmonary Responses of Wistar Kyoto, Spontaneously Hypertensive, and Stroke-prone Spontaneously Hypertensive Rats to Particulate Matter (PM) Exposure

Abstract

Humans with underlying cardiovascular disease, including stroke, are more susceptible to ambient particulate matter (PM)-induced morbidity and mortality. We hypothesized that stroke-prone spontaneously hypertensive rats (SHRSP) would be more susceptible than healthy Wistar Kyoto (WKY) rats to PM-induced cardiac oxidative stress and pulmonary injury. We further postulated that PM-induced injury would be greater in SHRSP than in spontaneously hypertensive rats (SHR) based on the greater disease severity in SHRSP than SHR. First, male WKY and SHRSP were intratracheally (IT) instilled with saline or 1.11, 3.33, or 8.33 mg/kg of oil combustion PM and responses were analyzed 4 or 24 h later. Second, SHR and SHRSP were IT instilled with saline or 3.33 or 8.33 mg/kg of the same PM and responses were analyzed 24 h later. Pulmonary injury and inflammation were assessed in bronchoalveolar lavage fluid (BALF) and cardiac markers in cytosolic and mitochondrial fractions. BALF neutrophilic inflammatory response was induced similarly in all strains following PM exposure. BALF protein leakage, γ-glutamyl transferase, and N-acetylglucosaminidase activities, but not lactate dehydrogenase activity, were exacerbated in SHRSP compared to WKY or SHR. Pulmonary cytosolic and cardiac mitochondrial ferritin levels decreased, and cardiac cytosolic superoxide dismutase (SOD) activity increased in SHRSP only. Pulmonary SOD activity decreased in WKY and SHRSP. Cardiac mitochondrial isocitrate dehydrogenase (ICDH) activity decreased in PM-exposed WKY and SHR; control levels were lower in SHRSP than SHR or WKY. In summary, strain-related differences exist in pulmonary protein leakage and oxidative stress markers. PM-induced changes in cardiac oxidative stress sensitive enzymes are small, and appear only slightly exacerbated in SHRSP compared to WKY or SHR. Multiple biological markers may be differentially affected by PM in genetic models of cardiovascular diseases. Preexisting cardiovascular disease may influence susceptibility to PM pulmonary and cardiac health effects in a disease-specific manner.

The authors thank Darrell Winsett and James Lehmann, both of the U.S. EPA, for performing the intratracheal instillations, and John Horton of NIEHS for his excellent technical assistance with TEM preparations. We thank Drs. Linda Birnbaum, Dan Costa, and James Samet of the U.S. EPA for critical review of this article. The HP12 bulk sample was provided by Drs. Russ Hauser and David Christiani of the Harvard School of Public Health. This work was supported in part by CT 829471, a cooperative training agreement between the U.S. EPA and the University of North Carolina at Chapel Hill.

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environ-mental Protection Agency, and NIEHS, and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the agencies, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.